Could vitamin C sensitise cancer cells to radiation?

The green light has been given to regularly infuse patients with brain and lung cancer with 800–1000 times the daily recommended amount of vitamin C as a potential strategy to improve outcomes of standard cancer treatments. University of Iowa researchers also show pathways by which altered iron metabolism in cancer cells, and not normal cells, leads to increased sensitivity to cancer cell death caused by high-dose vitamin C, presented in Cancer Cell.

Co-author Garry Buettner was one of the first to propose that cancer cells might have a vulnerability to redox active compounds over 40 years ago. “This paper reveals a metabolic frailty in cancer cells that is based on their own production of oxidising agents that allows us to utilise existing redox active compounds, like vitamin C, to sensitise cancer cells to radiation and chemotherapy,” he said.

Buettner, along with study senior authors Bryan Allen and Douglas Spitz, are faculty members at the University of Iowa’s Department of Radiation Oncology, Free Radical and Radiation Biology Program, in the Holden Comprehensive Cancer Center.

Eleven patients enrolled in the brain cancer safety trial received three infusions of vitamin C a week for 2 months followed by two infusions per week for 7 months while receiving standard care radiation and chemotherapy. The goal of each infusion was to raise the concentration of vitamin C in a patient’s blood to 20,000 µM, as compared to a blood level of about 70 µM found in most adults. The high dose is necessary because vitamin C has a half-life of about two hours in the circulation of humans. The treatment was generally well tolerated, with modest side effects including frequent trips to the bathroom and dry mouth. Rarely, some patients developed high blood pressure that subsided quickly following infusion.

Toxicity

Vitamin C, even at high levels, is not toxic to normal cells. The research group at Iowa found, however, that tumour tissue’s abnormally high levels of redox active iron react with vitamin C to form hydrogen peroxide and free radicals derived from hydrogen peroxide. These free radicals are believed to cause DNA damage selectively in cancer cells (versus normal cells) leading to enhanced cancer cell death as well as sensitisation to radiation and chemotherapy in cancer cells.

“This is a significant example of how knowing details of potential mechanisms and the basic science of redox active compounds in cancer versus normal cells can be leveraged clinically in cancer therapy,” said co-senior author Douglas Spitz, who focused on the biochemical studies. “Here, we verified convincingly that increased redox active metal ions in cancer cells were responsible for this differential sensitivity of cancer versus normal cells to very high doses of vitamin C.”

The safety study sets the stage for phase II clinical trials looking at whether high-dose vitamin C is effective at extending overall lifespan and quality of life for patients undergoing radiation and chemotherapy. The researchers are currently enrolling patients with stage 4 lung cancer and will soon begin enrolling people with glioblastoma multiforme (brain cancer) in these phase II trials. They are hopeful that brain cancer responses to radiation and chemotherapy can be enhanced in these phase II trials.

The phase I trial data showed an increase in overall survival of 4–6 months in 11 glioblastoma multiforme patients (18–22 months) versus the 14–16 months survival typically seen with the standard treatment.

“The majority of cancer patients we work with are excited to participate in clinical trials that could benefit future patient outcomes down the line,” said co-senior author Bryan Allen, who led the clinical side of the study. “Results look promising but we’re not going to know if this approach really improves therapy response until we complete these phase II trials,” he said.

Image credit: ©stock.adobe.com/au/Melpomene